Orfeh was born and raised in New York City. She attended the LaGuardia High School for the Performing Arts and received a record deal shortly after graduation. Her first release was Life in the Movies, which she released as a part of the group Genevha with her musical partner Mike More in 1987. After the release, the duo formed the group Or-N-More and signed with EMI Records.

In 1991, the duo released a self-titled album, their single "Everyotherday" reached number 46 on the Billboard Hot 100. The album was awarded gold status, but shortly after the album's success, the duo found out their Business manager had mis-managed their finances. She has been quoted about the situation, "My recording career went wrong," she has said. "Really, really wrong. We had the Business manager that stole all the money, the hit record that was about to become a mega-hit record and suddenly the rug was pulled out from under us. After being on the road for years and devoting my life to recording, I found myself at home saying, 'What do I do now?'"

Orfeh made her Broadway debut in 1998 as a swing in Footloose. In early 1999, Orfeh joined the ten-member company of The Gershwins 'Fascinating Rhythm' with Adriane Lenox, Sara Ramirez and Patrick Wilson. She then starred in the Original Broadway Company of London musical of Saturday Night Fever as Annette, and in addition to winning positive reviews, Orfeh met her husband, Andy Karl, while playing the role. In 1999, she appeared on The Rosie O'Donnell Show to promote the musical and perform her solo from the show, If I Can't Have You.

After Or-N-More disbanded, Orfeh signed a publishing deal with Warner/Chappell Music and continued to write and produce songs for other artists. She also remains a member of the National Academy of Recording Arts and Sciences, which gives her nominating and voting privileges for the Grammy Awards. She also co-wrote the song "Wishing On You," which appears on the Soundtrack of the Disney film Model Behavior that was released in 2000.

In 2001, she married actor Andy Karl, a three-time Tony nominated actor who she met during her performance in Saturday Night Fever, and played opposite her as Paulette's UPS man, Kyle in the original cast of Legally Blonde. The couple splits their time between New York City and Los Angeles.

Orfeh released her first solo album, What Do You Want from Me, on September 30, 2008. In 2014, Orfeh recorded a song for Michael Mott's album, "Where The Sky Ends" which was later released as a dance mix. In 2015, she released the Christmas-themed single Baby Please Come Home. In 2016, Orfeh and her husband performed at the Lincoln Center's American Songbook series. That same year, she was featured on the single What the World Needs Now is Love with other Broadway artists and released the solo single, Forget My Name.